药理学和生物有效性的重组,人性化,单链抗体C5补体抑制剂在接受冠状动脉搭桥手术的患者心肺旁路。
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惠誉JC,罗林斯,魅力匙L,阿尔弗德B, Aranki年代,羽衣甘蓝CD,杜瓦M, Elefteriades J,海恩斯R,科夫G, Kraker P,李L,奥哈拉R,果皮C,果皮H,肖R,史密斯B,斯塔尔G, Shernan SK
药理学和生物有效性的重组,人性化,单链抗体C5补体抑制剂在接受冠状动脉搭桥手术的患者心肺旁路。
循环。1999年12月第21至28,100 (25):2499 - 506。
- PubMed ID
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10604887 (在PubMed]
- 文摘
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背景:体外循环(CPB)诱发系统性炎症反应,导致大量的临床发病率。激活补体在CPB导致这种炎症过程的重要原因。我们检查了小说的功能治疗补体抑制剂防止病理补体的激活和组织损伤的患者接受心脏。方法和结果:人性化、重组单链抗体特定人类C5 h5G1.1-scFv,静脉注射1 4剂量之前从0.2到2.0毫克/公斤。h5G1.1-scFv被发现是安全的和良好的耐受性。药代动力学分析显示持续半衰期从7.0到14.5小时。药效学分析展示了明显的剂量依赖性抑制补体溶血活性长达14小时2毫克/公斤。代的促炎补副产品(sC5b-9)有效地抑制剂量依赖性的方式。白细胞激活,以表面CD11b的表达,减少(P < 0.05),病人1和2毫克/公斤。有40%的减少心肌损伤(肌酸kinase-MB释放,P = 0.05)病人2毫克/公斤。 Sequential Mini-Mental State Examinations (MMSE) demonstrated an 80% reduction in new cognitive deficits (P<0.05) in patients treated with 2 mg/kg. Finally, there was a 1-U reduction in postoperative blood loss (P<0. 05) in patients who received 1 or 2 mg/kg. CONCLUSIONS: A single-chain antibody specific for human C5 is a safe and effective inhibitor of pathological complement activation in patients undergoing CPB. In addition to significantly reducing sC5b-9 formation and leukocyte CD11b expression, C5 inhibition significantly attenuates postoperative myocardial injury, cognitive deficits, and blood loss. These data suggest that C5 inhibition may represent a novel therapeutic strategy for preventing complement-mediated inflammation and tissue injury.
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